This study examined the effects of acclimization to hypoxia (4559 m) on mitochondrial substrate utilization and respiratory function. The Bergstrom technique was used to obtain muscle biopsies of the vastus lateralis from 10 healthy Danish male subjects (25± 2 yrs) at sea level and again after 6 to 9 days at high altitude. High-resolution respirometry (Oroboros Oxygraph-2k [1]) allowed quantification of mitochondrial respiratory capacities from saponin-permeabilized skeletal muscle fibers (2-6 mg).

At sea level, state 3 respiration (in the presence of ADP) with parallel electron input into respiratory complexes I+II (glutamate, malate and succinate) was 58±4 pmol∙s-1∙mg-1), 1.6-fold higher than with glutamate+malate or succinate+rotenone. Flux with complex I+II substrates indicates the capacity of the phosphorylation system as shown by the 1.5-fold higher respiration after uncoupling by FCCP. These findings obtained with permeabilized muscle fibers agree with results on isolated mitochondria [2]. Respiratory capacity with octanoylcarnitine+malate was 48 % of that with glutamate+malate. Respiratory coupling was quantified through the stimulation by ADP or inhibition of ATP synthase by oligomycin and subsequent uncoupling by FCCP. Respiratory control ratios with succinate or octanoylcarnitine were 2.8. Compared to these results at sea level, 6 to 9 days of high altitude exposure did not induce a detectable change in any of the respiratory capacities nor in coupling. These findings indicate that mitochondrial function is not a limiting factor for VO2max during early acclimatization to high altitude, strengthening the concept of a dominant role for systemic oxygen delivery during intense dynamic exercise [3].

Funded by Fonds de la Recherche en Sante Québec (FRSQ), Research Chair, The Natural Science and Engineering Research Council of Canada (NSERC).